Histologic and morphometric analysis of the choroid, Bruch's membrane, and retinal pigment epithelium in postmortem eyes with age-related macular degeneration and histologic examination of surgically excised choroidal neovascular membranes

Abstract

Objective: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrialized countries. Different risk factors have been associated with AMD. We performed a histopathologic and morphometric study to compare eyes with different stages of AMD to age-matched eyes. This study aimed to investigate the correlation among morphometric characteristics of choroidal vessels, the retinal pigment epithelium, and Bruch's membrane, to study the association between these characteristics and the presence and type of AMD, and to identify morphologic risk factors for exudative AMD. Furthermore, we histologically analyzed surgically removed choroidal neovascular membranes secondary to underlying diseases other than AMD to discern whether the cellular and extracellular components of the membranes of eyes with AMD are similar to those with diseases other than AMD.

Methods: We analyzed 51 eye bank eyes (Georgia Eye Bank, Atlanta, GA) from 40 donors with different stages of AMD and compared them with 40 age-matched controls. The eyes were processed for light microscopy. The degree of calcification of Bruch's membrane, fragmentation of Bruch's membrane, number and types of drusen, basal laminar deposit, and seven morphometric variables of the choroid were assessed in the macular and extramacular regions. Surgically excised subfoveal membranes were processed and evaluated by light and transmission electron microscopy.

Results: There were no statistically significant differences observed between eyes with neovascular and non-neovascular AMD. The single most important difference between eyes with and without AMD was the amount of basal laminar deposit (P < 0.001). Eyes with AMD displayed fewer large choroidal vessels in the submacular choroid than eyes without AMD (mean density values of all choroidal vessels [arteries and veins] were 3.5 +/- 1.5 mm(-1) and 5.7 +/- 1.6 mm(-1), P < 0.001, respectively). The submacular choriocapillaris density was higher in eyes with AMD (mean density, 0.62 +/- 0.06) than in eyes without AMD (mean density, 0.51 +/- 0.08 [P < 0.001]). The diameter of the larger choroidal vessels in the peripheral choroid was higher in eyes with AMD (mean diameter, 30 +/- 8 microm) than in eyes without AMD (mean diameter, 21.4 +/- 6.2 microm [P < 0.001]). The peripheral choriocapillaris density displayed the same pattern as the macular region in eyes with and without AMD. There was a statistically significant difference observed in the degree of calcification and fragmentation of Bruch's membrane in eyes with exudative AMD (mean degree of calcification, 1.6; median number of breaks in Bruch's membrane, five) as compared with controls (mean degree of calcification, 0.8; median number of breaks in Bruch's membrane, zero). The difference for these two variables between eyes with nonexudative AMD (mean degree of calcification, 0.8; median number of breaks in Bruch's membrane, one) and controls (mean degree of calcification, 0.8; median number of breaks in Bruch's membrane, zero) failed to reach statistical significance. Eyes with AMD displayed significantly more soft, diffuse, and large drusen, as well as basal laminar deposit, in the macular area than controls.

Conclusion: Combining our data with data from the literature, we conclude that AMD can be interpreted as a dynamic process with early proliferation and subsequent atrophy of capillaries of the choriocapillaris. Calcification and fragmentation of Bruch's membrane; soft, diffuse, and large drusen; and basal laminar deposit, but not hard drusen, strongly correlate with the histologic presence of AMD. The degree of calcification and fragmentation of Bruch's membrane is prominent in eyes with exudative AMD. The formation of choroidal neovascular membranes represents a stereotypic, nonspecific wound repair response independent of the underlying disease.